Generating New Hope Through Pelotonia-Funded Research

Developing and testing therapeutic agents is costly and time-consuming, but these agents offer great promise for preventing, treating and curing cancer. Pelotonia funds support cancer drug development projects at Ohio State, including: an early-phase clinical trial on the safety of an anticancer vaccine designed to prevent the recurrence of several types of solid tumors; a phase II clinical trial of an experimental drug for patients with certain forms of leukemia; and a basic science study that has discovered how tamoxifen-resistant breast cancer cells grow and proliferate. Here’s a glance at each:

The vaccine trial, led by overall chair Pravin Kaumaya, PhD, and clinical co-principal investigators Tanios Bekaii-Saab, MD, and William Carson III, MD, has benefited some of the 12 cancer patients (two groups of six) who have received the vaccine since the trial opened at The James in July 2011. One component of the vaccine targets a molecule that occurs at abnormally high levels in up to 30 percent of breast cancers. Another component targets a molecule that is over-expressed in many other solid tumors, including ovarian, renal, colon, lung and gastrointestinal cancers. “The goals are to determine the safety and optimal dose of the vaccine, evaluate whether it shows therapeutic benefit by stimulating the immune system to respond to the patient’s tumor, and document any clinical responses that may occur,” Kaumaya says. The investigators report that four patients receiving the vaccine in group/dose level 1 had stable disease, while four patients in group/dose level 2 showed a partial response and three showed stable disease. Four patients have received a six-month booster so far.

The phase II clinical trial, open only at Ohio State, will determine the effectiveness of an experimental drug called PCI-32765 (ibrutinib) in treating patients with chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL) or B-cell prolymphocytic leukemia (B-PLL) who have not responded to or who have relapsed after standard treatment. Principal investigator Kami Maddocks, MD, says the drug involved in this trial, which opened in April 2012 and is recruiting patients, inhibits a certain protein that is believed to help blood cancer cells live and grow. “By inhibiting or ‘blocking’ the activity of this protein,” Maddocks says, “it is possible that the study drug may kill the cancer cells or stop them from growing.” The trial is studying all of the effects that treatment with this drug has on patients and their cancers.

The basic study that discovered how tamoxifen-resistant breast-cancer cells grow and proliferate also suggests that an experimental drug called vismodegib may offer a new targeted therapy for patients for whom tamoxifen therapy has failed. This study, published in the journal Cancer Research, showed that a signaling pathway called hedgehog (Hhg) can promote breast cancer cell growth after tamoxifen shuts down the pathway activated by the hormone estrogen, and that a second signaling pathway, called PI3K/ AKT, is also involved. The researchers, led by principal investigator Sarmila Majumder, PhD, and first author Bhuvaneswari Ramaswamy, MD, say activation of the Hhg pathway makes tamoxifen treatment ineffective, enabling the tumor to resume growth and progression. They analyzed more than 300 human tumors and found that those with an activated Hhg pathway had a worse prognosis. Finally, they showed that an experimental drug called vismodegib, which blocks the Hhg pathway, inhibits the growth of tamoxifen-resistant human breast tumors in an animal model. “Our findings suggest we can target this pathway in patients with estrogen-receptor breast cancers who have failed tamoxifen,” Ramaswamy says, noting that 30-40 percent of patients taking tamoxifen become resistant to it after about five years. “Our next step is to organize a clinical trial to evaluate vismodegib in patients with tamoxifen-resistant breast cancer.”